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制备用于万古霉素递送和三维细胞培养的氧化结冷胶/明胶可注射水凝胶。

forming oxidized salecan/gelatin injectable hydrogels for vancomycin delivery and 3D cell culture.

作者信息

Fan Zhiping, Cheng Ping, Yin Gaowei, Wang Zhengping, Han Jun

机构信息

Institute of BioPharmaceutical Research, Liaocheng University, Liaocheng, China.

Liaocheng High-Tech Biotechnology Co., Ltd, Liaocheng, China.

出版信息

J Biomater Sci Polym Ed. 2020 Apr;31(6):762-780. doi: 10.1080/09205063.2020.1717739. Epub 2020 Jan 28.

Abstract

Antibiotics are widely used in clinical medicine. As an important member, vancomycin often plays an irreplaceable role in some serious infections, but its use still lacks suitable carriers and effective formulations. In order to find a vancomycin carrier with potential for clinical application, a new class of oxidized salecan/gelatin based injectable hydrogels are constructed through dynamic covalent Schiff base reaction. The sodium periodate oxidized salecan (OS) precursor was synthesized, and then the gelatin/oxidized salecan (GS) hydrogels are formed by blending gelatin and OS buffer solutions without any additives under physiological condition. The chemical structure, as well as internal morphologies, mechanical properties, enzymatic degradation profile of hydrogels are investigated with proton nuclear magnetic resonance (H NMR), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), compression test and rheological experiments. The resulted hydrogels exhibit excellent antibacterial ability and variable characteristics. Moreover, the hydrogels display ideal drug release kinetics and mechanisms, and are applied successfully to the controlled release of vancomycin. Importantly, benefitting from the excellent biocompatibility and the reversibly crosslinked networks, GS hydrogels can function as suitable three dimensional (3D) extracellular matrix for HeLa cells, leading to the encapsulated cells maintaining a high viability and proliferative capacity. Therefore, the injectable GS hydrogels demonstrated attractive properties for future application in pharmaceutics and tissue engineering.

摘要

抗生素在临床医学中被广泛使用。作为重要成员之一,万古霉素在一些严重感染中常常发挥着不可替代的作用,但其使用仍缺乏合适的载体和有效的制剂。为了找到一种具有临床应用潜力的万古霉素载体,通过动态共价席夫碱反应构建了一类新型的基于氧化结冷胶/明胶的可注射水凝胶。合成了高碘酸钠氧化结冷胶(OS)前体,然后在生理条件下将明胶与OS缓冲溶液混合,无需任何添加剂即可形成明胶/氧化结冷胶(GS)水凝胶。通过质子核磁共振(H NMR)、傅里叶变换红外光谱(FTIR)、扫描电子显微镜(SEM)、压缩试验和流变学实验研究了水凝胶的化学结构、内部形态、力学性能和酶降解特性。所得水凝胶表现出优异的抗菌能力和可变特性。此外,水凝胶显示出理想的药物释放动力学和机制,并成功应用于万古霉素的控释。重要的是,得益于优异的生物相容性和可逆交联网络,GS水凝胶可作为适合HeLa细胞的三维(3D)细胞外基质,使包封的细胞保持高活力和增殖能力。因此,可注射的GS水凝胶在药物制剂和组织工程的未来应用中显示出诱人的特性。

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